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Gastroenterology. 2002 Jul;123(1):227-34.

Endocannabinoids as physiological regulators of colonic propulsion in mice.

Author information

1
Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy.

Abstract

BACKGROUND & AIMS:

Activation of enteric cannabinoid CB1 receptors inhibits motility in the small intestine; however, it is not known whether endogenous cannabinoids (anandamide and 2-arachidonylglycerol) play a physiologic role in regulating intestinal motility. In the present study, we investigated the possible involvement of endocannabinoids in regulating intestinal propulsion in the mouse colon in vivo.

METHODS:

Intestinal motility was studied measuring the expulsion of a glass bead inserted into the distal colon; endocannabinoid levels were measured by isotope-dilution gas chromatography-mass spectrometry; anandamide amidohydrolase activity was measured by specific enzyme assays. CB1 receptors were localized by immunohistochemistry.

RESULTS:

Anandamide, WIN 55,212-2, cannabinol (nonselective cannabinoid agonists), and ACEA (a selective CB1 agonist) inhibited colonic propulsion; this effect was counteracted by SR141716A, a CB1 receptor antagonist. Administered alone, SR141716A increased motility, whereas the inhibitor of anandamide cellular reuptake, VDM11, decreased motility. High amounts of 2-arachidonylglycerol and particularly anandamide were found in the colon, together with a high activity of anandamide amidohydrolase. CB1 receptor immunoreactivity was colocalized to a subpopulation of choline acetyltransferase-immunoreactive neurons and fiber bundles in the myenteric plexus.

CONCLUSIONS:

We conclude that endocannabinoids acting on myenteric CB1 receptors tonically inhibit colonic propulsion in mice.

PMID:
12105851
DOI:
10.1053/gast.2002.34242
[Indexed for MEDLINE]

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